Dr Christos Tziotzios on his BSF-funded research into frontal fibrosing alopecia (FFA)

May 2020

About Dr Tziotzios

Dr Tziotzios graduated from the University of Cambridge. He undertook Integrated Academic Training as NIHR Academic Clinical Fellow in Dermatology at St. John’s where he developed an interest in molecular genetic research and hair disorders. He secured substantial research grant funding to undertake doctoral research into dissecting the molecular pathogenesis of frontal fibrosing alopecia (FFA), a highly distressing type of scarring hair loss affecting almost exclusively women. His PhD research at St. John’s has culminated in high-impact publications, including an original article in Nature Communications, and several distinctions such as the BAD Whimster Prize, the RSM Research Prize and the NIHR/BAD Award.

The impact of hair loss and frontal fibrosing alopecia (FFA)

The impact of hair loss, especially in women, can be profound. Hair loss can be non-scarring (such as androgenetic alopecia or alopecia areata) or scarring, with the former being potentially reversible whilst the latter is irreversible.

FFA is a T cell-driven alopecia, which is considered to be a clinical variant of follicular lichen planus, also known as lichen planopilaris (LPP). LPP is regarded as the prototypic primary lymphocytic scarring alopecia and is the scalp counterpart of the commoner lichen planus, which affects other body parts. FFA is one of many scarring alopecias, which are known to be irreversible. This is because the cells (which are known as stem cells) responsible for regenerating the hair follicle are destructed by the inflammation. It is therefore important to stop the inflammation as early as possible to prevent permanent scarring hair loss.

Since FFA was first identified by Kossard in 1994, there has been a rapid increase in the incidence of the condition and this has led to intense clinical and public interest in the condition. FFA is often referred to as a dermatological epidemic with possible environmental trigger(s) implicated in addition to a genetic basis.

A better understanding of the molecular basis of FFA and its interplay with environmental risk factors could thus provide insight into lichenoid inflammation, scarring and mechanisms of stem cell destruction. Furthermore, the identification of environmental triggers that interact with genes underpinning FFA could ultimately contribute to disease prevention by avoidance of exposures in genetically predisposed individuals.

Background work

Our recently published large-scale study of the molecular genetic basis of FFA was the first systematic investigation into the molecular basis of FFA or any other lichenoid inflammatory disorder. We hypothesised that common genetic variation contributes to FFA and undertook a genome-wide association study (GWAS) in females from a UK cohort, comprising 844 cases and 3,760 controls, a Spanish cohort of 172 cases and 385 controls, and performed statistical meta-analysis. We observed and reported highly robust and significant association with a number of genes related to immune response, T-cells and also hormonal drug metabolism. We also looked at gene expression in affected scalp skin tissue biopsies and discovered that certain pathways (such as the Janus kinase and interferon-gamma pathways) are very relevant to the disease and therefore targeting these may help in the discovery of new treatments.

Our findings suggested that FFA has a strong genetic basis and is of autoimmune nature with involvement of hormonal drug exposure and their metabolism. Additional lines of evidence implicating exposure to hormonal contraception as a potential risk factor is also emerging from an ongoing study of discordant monozygotic twins. Taken together, alongside the temporal relationship between the introduction of oral contraceptives (a female-specific CYP1B1 substrate) in the 1960s and the appearance of FFA in the published literature in the 1990s, prompted us to pursue the notion further: a preliminary case-only gene-environment interaction analysis of the CYP1B1 variant in 736 cases showed support for an interaction between CYP1B1 and exposure to hormonal contraception (P=0.016).

Ongoing work:

The Young Investigator Award from the British Skin Foundation will enable me to explore how exposure to hormonal drugs might interact with the metabolic enzyme-encoding gene CYP1B1 in causing FFA. This will be accomplished by undertaking a case-control gene-environment interaction analysis.

In addition, we will continue to expand our European female FFA cohort via strengthening our collaborative links with academic centres in Germany, Spain, Italy and Greece with a view to undertake a larger-scale meta-GWAS. We anticipate that this will help us understand any of the 28 loci, which we identified as loci of suggestive genome-wide significance, are truly associated with FFA.

Finally, we are hoping to build a bio-resource of human hair follicular units to help us accomplish a study linking gene expression with genetic variation. Such an open-access resource will help future functional genomic work in the field of hair follicle and stem cell research.

How this research may help patients

Increasing our understanding of the genetic basis of the condition may enable us to devise genetic risk scoring tools, which may allow us to predict who might be at risk of developing the condition. Concurrently, identifying environmental factors associated with FFA may well help prevent people from developing the disease, depending on the actual contribution of such factors. Finally, our research may also provide guidance into novel and better treatments: our previous work provided molecular evidence for the use of a new class of drugs (targeting the Janus kinase pathway), a treatment approach which has already been found to be beneficial in a preliminary study.

We'd love to keep you posted with our news, activities and how you can help in other ways. We'll never sell or swap your details with anybody else. You are free to change your mind at anytime. Please indicate how you would like to hear from us by using the tick boxes below

Your Privacy

We will always store your personal details securely. We'll use them to provide the service that you have requested, and communicate with you in the way(s) that you have agreed to. Your data may also be used for analysis purposes, to help us provide the best service possible. For full details see our Privacy Policy

The British Skin Foundation website is comprised of various web pages operated by the British Skin Foundation.

The British Skin Foundation website is offered to you conditioned on your acceptance without modification of the terms, conditions, and notices contained herein. Your use of the British Skin Foundation website constitutes your agreement to all such terms, conditions, and notices.

Modification of these terms of use

The British Skin Foundation reserves the right to change the terms, conditions, and notices under which the British Skin Foundation website is offered, including but not limited to the charges associated with the use of the British Skin Foundation website

Links to third party sites

The British Skin Foundation website may contain links to other website ("linked Sites"). The linked sites are not under the control of the British Skin Foundation and the British Skin Foundation is not responsible for the contents of any linked site, including without limitation any link contained in a linked site, or any changes or updates to a linked site. The British Skin Foundation is not responsible for webcasting or any other form of transmission received from any linked site. The British Skin Foundation is providing these links to you only as a convenience, and the inclusion of any link does not imply endorsement by the British Skin Foundation of the site or any association with its operators.

No unlawful or prohibited use

As a condition of your use of the British Skin Foundation website, you warrant to the British Skin Foundation that you will not use the British Skin Foundation website for any purpose that is unlawful or prohibited by these terms, conditions, and notices. You may not use the British Skin Foundation website in any manner which could damage, disable, overburden, or impair the British Skin Foundation Web Site or interfere with any other party's use and enjoyment of the British Skin Foundation website. You may not obtain or attempt to obtain any materials or information through any means not intentionally made available or provided for through the British Skin Foundation website.

Use of communication services

The British Skin Foundation website may contain bulletin board services, chat areas, news groups, forums, communities, personal web pages, calendars, and/or other message or communication facilities designed to enable you to communicate with the public at large or with a group (collectively, "communication services"), you agree to use the communication services only to post, send and receive messages and material that are proper and related to the particular communication service. By way of example, and not as a limitation, you agree that when using a communication service, you will not:

Defame, abuse, harass, stalk, threaten or otherwise violate the legal rights (such as rights of privacy and publicity) of others.Publish, post, upload, distribute or disseminate any inappropriate, profane, defamatory, infringing, obscene, indecent or unlawful topic, name, material or information.Upload files that contain software or other material protected by intellectual property laws (or by rights of privacy of publicity) unless you own or control the rights thereto or have received all necessary consents.Upload files that contain viruses, corrupted files, or any other similar software or programs that may damage the operation of another's computer.Advertise or offer to sell or buy any goods or services for any business purpose, unless such communication service specifically allows such messages.Conduct or forward surveys, contests, pyramid schemes or chain letters.Download any file posted by another user of a communication service that you know, or reasonably should know, cannot be legally distributed in such manner.Falsify or delete any author attributions, legal or other proper notices or proprietary designations or labels of the origin or source of software or other material contained in a file that is uploaded.Restrict or inhibit any other user from using and enjoying the communication services.Violate any code of conduct or other guidelines which may be applicable for any particular communication service.Harvest or otherwise collect information about others, including e-mail addresses, without their consent.Violate any applicable laws or regulations.The British Skin Foundation has no obligation to monitor the communication services. However, the British Skin Foundation reserves the right to review materials posted to a communication service and to remove any materials in its sole discretion. The British Skin Foundation reserves the right to terminate your access to any or all of the communication services at any time without notice for any reason whatsoever.The British Skin Foundation reserves the right at all times to disclose any information as necessary to satisfy any applicable law, regulation, legal process or governmental request, or to edit, refuse to post or to remove any information or materials, in whole or in part, in The British Skin Foundation's sole discretion.Always use caution when giving out any personally identifying information about yourself or your children in any communication service. The British Skin Foundation does not control or endorse the content, messages or information found in any communication service and, therefore, the British Skin Foundation specifically disclaims any liability with regard to the communication services and any actions resulting from your participation in any communication service. Managers and hosts are not authorised the British Skin Foundation spokespersons, and their views do not necessarily reflect those of the British Skin Foundation.Materials uploaded to a communication service may be subject to posted limitations on usage, reproduction and/or dissemination. You are responsible for adhering to such limitations if you download the materials.Materials provided to the British Skin Foundation or posted at any the British Skin Foundation website.The British Skin Foundation does not claim ownership of the materials you provide to the British Skin Foundation (including feedback and suggestions) or post, upload, input or submit to any the British Skin Foundation website or its associated services (collectively "submissions"). However, by posting, uploading, inputting, providing or submitting your Submission you are granting the British Skin Foundation, its affiliated companies and necessary sublicensees permission to use your submission in connection with the operation of their internet businesses including, without limitation, the rights to: copy, distribute, transmit, publicly display, publicly perform, reproduce, edit, translate and reformat your Submission; and to publish your name in connection with your submission.No compensation will be paid with respect to the use of your submission, as provided herein. The British Skin Foundation is under no obligation to post or use any submission you may provide and may remove any submission at any time in The British Skin Foundation's sole discretion.By posting, uploading, inputting, providing or submitting your submission you warrant and represent that you own or otherwise control all of the rights to your Submission as described in this section including, without limitation, all the rights necessary for you to provide, post, upload, input or submit the submissions.

Liability disclaimer

The information, software, products, and services included in or available through the British Skin Foundation website may include inaccuracies or typographical errors. Changes are periodically added to the information herein. The British Skin Foundation and/or its suppliers may make improvements and/or changes in the British Skin Foundation website at any time. Advice received via the British Skin Foundation website should not be relied upon for personal, medical, legal or financial decisions and you should consult an appropriate professional for specific advice tailored to your situation.

The British Skin Foundation and/or its suppliers make no representations about the suitability, reliability, availability, timeliness, and accuracy of the information, software, products, services and related graphics contained on the British Skin Foundation website for any purpose. To the maximum extent permitted by applicable law, all such information, software, products, services and related graphics are provided "as is" without warranty or condition of any kind. The British Skin Foundation and/or its suppliers hereby disclaim all warranties and conditions with regard to this information, software, products, services and related graphics, including all implied warranties or conditions of merchantability, fitness for a particular purpose, title and non-infringement.

To the maximum extent permitted by applicable law, in no event shall the British Skin Foundation and/or its suppliers be liable for any direct, indirect, punitive, incidental, special, consequential damages or any damages whatsoever including, without limitation, damages for loss of use, data or profits, arising out of or in any way connected with the use or performance of the British Skin Foundation website, with the delay or inability to use the British Skin Foundation website or related services, the provision of or failure to provide services, or for any information, software, products, services and related graphics obtained through the British Skin Foundation website, or otherwise arising out of the use of the British Skin Foundation website, whether based on contract, tort, negligence, strict liability or otherwise, even if the British Skin Foundation or any of its suppliers has been advised of the possibility of damages. Because some states/jurisdictions do not allow the exclusion or limitation of liability for consequential or incidental damages, the above limitation may not apply to you. If you are dissatisfied with any portion of the British Skin Foundation website, or with any of these terms of use, your sole and exclusive remedy is to discontinue using the British Skin Foundation website.

The British Skin Foundation reserves the right, in its sole discretion, to terminate your access to the British Skin Foundation website and the related services or any portion thereof at any time, without notice.

The names of actual companies and products mentioned herein may be the trademarks of their respective owners.The example companies, organizations, products, people and events depicted herein are fictitious. No association with any real company, organization, product, person, or event is intended or should be inferred.

Any rights not expressly granted herein are reserved.

Sorry! That email/password combination cannot be found

Thank you! We have sent you an email to verify your account. Your comment will be published, subject to approval, after you have confirmed your email address.

Thank you! Your comment is waiting for approval and we will let you know when it goes live.

A squamous cell carcinoma is a type of skin cancer. There are two main types of skin cancer: melanoma and non-melanoma skin cancer. Squamous cell carcinoma (SCC) is a non-melanoma skin cancer (NMSC), and the second most common type of skin cancer in the UK.

Your donation will help us to fund research into all types of skin diseases, including potential killers like melanoma skin cancer. Skin diseases can affect everyday life, mental health, relationships and work-life. By donating towards our research, you’ll be helping to find cures and treatments that can dramatically improve the quality of life of someone with a skin condition.
Read more